You are here

Study Warns of Alzheimer’s Risk in Some Prostate-Cancer Drugs

Men taking testosterone-blocking drugs to treat prostate cancer have nearly twice the risk of developing Alzheimer’s disease as those using other treatments, according to an analysis of electronic medical records published Monday.

Androgen-deprivation therapy—also known as chemical castration—lowers levels of testosterone and other male hormones that can fuel the growth of prostate cancer. However, it has been linked to a higher risk of cardiovascular disease, diabetes, high cholesterol, impotence, loss of muscle mass, depression, breast growth and hot flashes in men. And several studies show that it doesn’t improve survival rates for men with localized prostate cancer.

Still, some 500,000 U.S. men are taking the drugs for prostate cancer, according to the study—in part, experts say, because they want to do something and may not be candidates for surgery or radiation.

Otis Brawley, chief medical officer of the American Cancer Society, who wasn’t involved in the study, said the study reinforced his longtime view that “we should be incredibly rigorous in deciding who should get hormonal therapy and who should not.”

Androgen deprivation has been used to treat metastatic prostate cancer since the 1940s, and studies have shown it can improve survival when used with radiation for men with tumors that have a high risk of spreading. But the drugs aren’t recommended for the far-larger group of men with localized, low-risk cancers. Experts say that in many cases, those tumors are so slow-growing that they could go untreated and not cause symptoms in the patient’s lifetime.

Use of anti-androgen drugs, including Lupron, Zoladex and Eligard, surged in the 1990s, which some critics attributed to high reimbursement rates for urologists who administered the injections. According to a study in the New England Journal of Medicine, when Medicare reimbursements for the drugs were cut by 40% in 2003, their use dropped from 39% to 26% of men with localized prostate cancer in 2005.

Use of anti-androgen drugs has continued to decline in such patients—to less than 10% in 2009—as more men with low-risk tumors have opted for active surveillance instead, according to a study in European Urology last year.

Overall sales of anti-androgen drugs, however, continue to climb.

For the latest study, which was published in the Journal of Clinical Oncology, researchers at Stanford and the University of Pennsylvania searched electronic medical records from Stanford Health Care in Palo Alto, Calif., and Mount Sinai Hospital in New York City. They identified 16,888 patients with non-metastatic prostate cancer between 1994 and 2013. Of those, nearly 2,400 were treated with anti-androgen therapy, and they had an 88% higher risk of being diagnosed with Alzheimer’s disease in the next three years than those who weren't. A subset of patients who received the therapy for longer than 12 months had more than twice the risk.

Men treated with hormone therapy tend to be older and sicker than those who have surgery or radiation, but the authors say they adjusted for such factors.

The authors also noted that while the study is the first to link anti-androgen therapy to Alzheimer’s disease, testosterone has been shown to aid the growth of brain cells and modulate the accumulation of B-amyloid protein, the main component of the amyloid plaques seen in Alzheimer’s patients. Low testosterone levels are also associated with higher rates of diabetes, stroke and heart disease, which increase the risk of Alzheimer’s.

Quoc-Dien Trinh, a urologist at Brigham and Women’s Hospital in Boston who wasn’t involved in the latest study, said that anti-androgen drugs can extend survival when used along with radiation in some cases. But he said the study was further evidence that “we should never use androgen-deprivation therapy alone for localized prostate cancer.”

Besides quantifying the increased risk of Alzheimer’s in such patients, the authors stressed that the study demonstrated how electronic medical records can be used to facilitate research. “We can’t do a randomized controlled trial for everything, but for questions that clinicians and patients have, we can shed some light using data-mining,” said Nigam H. Shah, senior author of the study.

By 

MELINDA BECK